Compared with patients with CH, those having MUCH had longer hypertension duration at baseline. There was no significant difference in CKD stages between the two groups. Notably, LVH was more prevalent in the MUCH group. All laboratory results did not have a statistically significant difference in the two groups (Table 1).

The difference between office and ambulatory BP in the two groups was statistically significant, with the BP values being higher in the MUCH group (Table 2). The rate of MUCH on 24-hour BP, daytime BP, and nighttime BP were 21.9%, 11.8%, and 48.9%, respectively, and based on all three criteria above was 48.9% (Table 1).

Table 2

Blood pressure (mmHg)	All (n = 178)	MUCH (n = 87)	CH (n = 91)	P-value
Office SBP	128.6 ± 6.2	130.4 ± 5.9	126.8 ± 6	< 0.001
Office DBP	73.9 ± 7.0	75.6 ± 6.7	72.3 ± 7.0	0.002
24-hour	118.7 ± 12.0	128.1 ± 8.1	109.6 ± 7.3	< 0.001
24-hour DBP	66.7 ± 7.9	70.6 ± 7.9	63.0 ± 5.8	< 0.001
SBP day	120.1 ± 11.5	128.3 ± 8.5	112.2 ± 8.0	< 0.001
DBP day	67.8 ± 8.0	71.1 ± 8.2	64.7 ± 6.5	< 0.001
SBP night	116.0 ± 14.7	128.0 ± 9.3	104.5 ± 8.3	< 0.001
DBP night	64.9 ± 9.0	70.3 ± 8.6	59.8 ± 5.9	< 0.001

Abbreviations: BP: blood pressure, SBP: systolic blood pressure, DBP: diastolic blood pressure, CH: controlled hypertension, MUCH: masked uncontrolled hypertension

As shown in univariate analysis, CKD stage 4-5 and MUCH were associated with LVH (OR = 2.64, 95% CI: 1.29 – 5.61, P = 0.009 and OR = 1.97, 95% CI: 1.09 – 3.60, P = 0.026, respectively) (Table 3). Both factors remained statistically significant when included in multivariate analysis. Patients with CKD stage 4-5 had a higher risk of LVH (OR = 2.58; 95% CI: 1.16 – 5.94, P = 0.036) while MUCH patients were at increased risk of LVH two times higher (OR = 1.97; 95% CI: 1.03 – 3.85, P = 0.026) (Table 3).

Table 3

	Univariate			Multivariate
	OR	CI 95%	P-value	OR	CI 95%	P-value
Age	1.16	0.48 – 2.86	0.746	--	--	--
Male	0.58	0.32 – 1.06	0.077	--	--	--
Current smoker	1.34	0.72 – 2.51	0.359	--	--	--
Diabetes mellitus	1.32	0.72 – 2.47	0.374	--	--	--
HTN duration ≥ 10 years	1.16	0.64 – 2.11	0.622	--	--	--
RAAS inhibitors	0.70	-1.00 – 0.29	0.286	--	--	--
Other HTN drugs	1.88	-0.33 – 1.589	0.199	--	--	--
CKD staging 4-5	2.64	1.29 – 5.61	0.009	2.58	1.16 – 5.94	0.036
MUCH	1.97	1.09 – 3.60	0.026	1.97	1.03 – 3.85	0.026

Abbreviations: LVH: left ventricular hypertrophy, HTN: hypertension, RAAS: renin-angiotensin-aldosterone system, CKD: chronic kidney disease, MUCH: masked uncontrolled hypertention

We used daytime and/or nighttime and/or 24-hour BP values to define MUCH and confirmed the rate was 48.9%. Other studies demonstrated that the prevalence of MUCH in CKD patients ranges from 45.0 to 70.0% depending on diagnostic criteria3, 5, 9. All patients participating in this study had elevated nocturnal BP while only 11.8% had high daytime BP. This finding suggested that the routine use of office BP measurement and even home BP monitoring had a limited role in detecting MUCH in patients with CKD. Though 24-hour ABPM does not provide day-to-day BP variations, this is a favorable approach in clinical settings for BP evaluation.

The precise mechanism by which CKD elevates nocturnal BP involves complex processes, including volume-dependent hypertension exacerbated by serum sodium dysregulation, comorbidities like diabetes mellitus, and autonomic nervous dysfunction10, 11, 12. The dysfunction of endothelial cells lowers nitric oxide production causing suppression of the sympathetic nervous system13. Nocturnal hypertension is common in individuals with CKD due to disruptions in the body's circadian rhythm as well. Fukuda et al. suggested that decreased renal function reduces sodium excretion during the day and nighttime BP then rises to increase sodium clearance14.

Our results are similar to the AASKD report, in which participants with masked hypertension had higher LVH proportions than those with normal BP and white-coat hypertension3. In the CRIC study, masked hypertension was associated with increased LVMI and pulse wave velocity compared to those with truly controlled BP4. LVH in individuals with CKD results from increased volume and pressure loads. Factors such as activation of the RAAS, inhibition of nitric oxide synthesis, intravascular volume expansion, secondary anemia, and arteriovenous fistulas contribute to myocardial cell elongation and the development of eccentric or asymmetric LVH, potentially progressing to LV fibrosis15. Clinical evidence underscores the association between LVH, myocardial fibrosis, and heightened mortality risk, along with increased cardiovascular events in CKD and ESRD, as evidenced by elevated rates of sudden cardiac death15. Regression of left ventricular mass could serve as a valuable surrogate marker for assessing the benefits of RAAS inhibition aimed at reducing mortality risk in hypertensive patients16. Similar results were observed in the CKD population with the roles of proper hemoglobin targets and hemodialysis regimens in addition to RAAS inhibition17.

A remarkable insight of our study is the use of 24-hour ambulatory BP for diagnosing out-of-office hypertension and assessing the BP patterns of patients with CKD. The prevalence of MUCH in the CKD population was considerable. Moreover, our findings support that CKD patients with MUCH have a higher risk of left ventricular hypertrophy than those with CH. Further studies are needed to define this relationship clearly and whether targeting MUCH patients can reduce the adverse outcomes.

There are several limitations of our study. First, due to limited resources, we did not assess sleep quality and other essential factors, including lifestyle choices and socioeconomic status, which have been proven to affect nocturnal BP, CKD, and LVH and their relationships18. Second, the study did not include those with structural CKD stages 1 and 2. Third, the retrospective design might introduce selection and information biases, as data were obtained from medical records. Fourth, while a sample size of 178 patients is adequate, a larger cohort that includes regional variations in patient demographics could yield more robust data. Fifth, the accuracy measurements may be influenced by equipment limitations regarding ABPM devices and variations in operator technique during the heart ultrasound. Future research should overcome these limitations by incorporating multicenter designs, recruiting larger and more diverse populations, and conducting longitudinal follow-ups to validate these findings.

We recommend routinely using ABPM, which is sustainable in developing countries like Vietnam, to detect MUCH, especially nocturnal high blood pressure in CKD patients even with controlled office hypertension. Screening for LVH is necessary in those with MUCH.

ABPM: Ambulatory Blood Pressure Monitoring, ACE: Angiotensin-Converting Enzyme, ARB: Angiotensin Receptor Blocker, BMI: Body Mass Index, BP: Blood Pressure, CCB: Calcium Channel Blocker, CH: Controlled Hypertension, CI: Confidence Interval, CKD: Chronic Kidney Disease, CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration, CRIC: Chronic Renal Insufficiency Cohort Study, DBP: Diastolic Blood Pressure, eGFR: Estimated Glomerular Filtration Rate, ESRD: End-Stage Renal Disease, HDL: High-Density Lipoprotein, HTN: Hypertension, LDL: Low-Density Lipoprotein, LVH: Left Ventricular Hypertrophy, LVEF: Left Ventricular Ejection Fraction, LVM: Left Ventricular Mass, LVMI: Left Ventricular Mass Index, MUCH: Masked Uncontrolled Hypertension, OR: Odds Ratio, RAAS: Renin-Angiotensin-Aldosterone System, SBP: Systolic Blood Pressure, SD: Standard Deviation

None.

All authors equally contributed to this work, read and approved the final manuscript.

None.

Data and materials used and/or analyzed during the current study are available from the corresponding author on reasonable request.

The study was approved by the ethics committee of the University of Medicine and Pharmacy at Ho Chi Minh City (No. 373/IRD/UMP, October 25, 2018) and written informed consent was obtained from all patients prior to enrollment. The investigation conformed to the principles outlined in the 1975 Declaration of Helsinki.

Not applicable.

The authors declare that they have no competing interests.